Ivacaftor May Be Effective for Infants With Cystic Fibrosis and Gating Mutation

Cystic fibrosis CAT scan
Cystic fibrosis CAT scan
Ivacaftor was safe and associated with improvements in cystic fibrosis transmembrane conductance regulator function in infants with CF and a gating mutation.

Treatment with ivacaftor was safe and associated with improvements in cystic fibrosis (CF) transmembrane conductance regulator (CFTR) function in infants between 4 and 12 months of age with CF and a gating mutation, according to study results published in the American Journal of Respiratory and Critical Care Medicine.

Investigators conducted a phase 3, single-arm, multicenter clinical trial (ARRIVAL; ClinicalTrials.gov Identifier: NCT02725567) that included 25 infants aged 12 months or younger with a confirmed diagnosis of CF and a CFTR gating mutation on 1 or more allele. Infants from US sites with an R117H mutation were also included in this study. The infants were treated with either 25 mg or 50 mg ivacaftor every 12 hours, depending on their age and weight, for a total of 4 days (part A; n=12) or 23 weeks (part B; n=17). A total of 4 infants participated in both parts A and B.

Safety was assessed in parts A and B, whereas pharmacokinetics associated with therapy was assessed in part A. Additional secondary and tertiary end points for part B were pharmacokinetics and changes in growth, markers of pancreatic function, and levels of sweat chloride.

The investigators found that the treatment had a pharmacokinetics profile consistent with that observed in older children and adults. No high plasma drug concentrations or exposures exceeding the range of prior clinical experience were reported.

Adverse events (AEs) were mostly mild/moderate in severity. Cough was the most common AE in part B (58.8%). Serious AEs were reported in 8.3% of infants in part A and 23.5% of patients in part B. The investigators considered all serious AEs as not or unlikely related to treatment. In addition, there were no deaths or discontinuations during the study.

Alanine transaminase elevation more than 3 and less than or equal to 5 times the upper limit of normal occurred in 1 infant at week 24. Despite this event, there were no other adverse trends in vital signs, laboratory tests, or electrocardiogram parameters.

During treatment, there were improvements in sweat chloride levels (mean absolute change from baseline to week 24, -55.7 mmol/L) and measures of endocrine pancreatic function (mean absolute change in fecal elastase-1 from baseline to week 24, 166.0 μg/g). The researchers wrote that improvements in pancreatic function indicate ivacaftor may minimize or delay progression exocrine pancreatic dysfunction observed in these patients.

Limitations of the study included the single-arm design as well as the small sample size, both of which the researchers suggested was related to the rarity of the disease.

The investigators concluded that their findings “support treating the underlying cause of CF in children aged ≥4 months.”

Disclosure: This clinical trial was supported by Vertex Pharmaceuticals. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Davies JC, Wainwright CE, Sawicki GS, et al; on behalf of the ARRIVAL Study Group Ivacaftor in infants aged 4 to <12 months with cystic fibrosis and a gating mutation: results of a 2-part phase 3 clinical trial. Published online October 7, 2020. Am J Respir Crit Care Med. doi:10.1164/rccm.202008-3177OC